Optically active carboxylic acids represented by the formula ##STR2## wherein R.sub.1 is hydrogen or ##STR3## R.sub.2 and R.sub.3 are each independently selected from alkyl, cycloalkyl, aralkyl or aryl, and n is 1 or 2, are useful, for example, as intermediates for the synthesis of various physiologically active materials. For example, compounds of the formula ##STR4## can each serve as a key intermediate in the synthesis of 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline (captopril), having the formula and [1(R*),2.alpha.,4.alpha.]-1-[3-(Benzoylthio)-2-methyl-1-oxopropyl]-4-(phen ylthio)-L-proline (zofenopril), having the formula ##STR5## The beneficial activity of captopril and zofenopril depends on the configuration of the mercaptoalkanoyl moiety and the compounds of the S configuration are about 100 times more potent than the corresponding R-enantiomers. Thus, the S-enantiomers illustrated by formula I are much more desirable for these purposes than their R-enantiomer counterparts.
Prior art processes for making captopril and zofenopril have utilized chemical and enzymatic resolution procedures. For example, carboxylic acids of the formula ##STR6## are prepared as racemic mixtures which can be separated into the R and S-enantiomeric forms using chemical resolving agents. The so-provided S intermediates can then be used to prepare the desired products. The chemical resolution techniques have the distinct disadvantage, however, that large amounts of very expensive resolving agents are required. Additionally, the processes themselves are cumbersome and the yield is relatively low.
Alternatively, racemic compounds of the formula ##STR7## can be directly coupled to X (which is L-proline in the case of captopril, and L-4-phenylthioproline in the case of zofenopril) to produce diastereomers of the general formula ##STR8## The SS-diastereomer of compound VI can be-isolated. Thereafter the sulfhydryl or benzoylthio groups corresponding to captopril and zofenopril, respectively, can be provided to the left side of the molecule by known methods. However, a drawback to this process is that an equal amount of the RS-diastereomer of compound VI is formed which must be discarded. This is highly undesirable in view of the cost of the L-proline and derivatives thereof.
U.S. Pat. No. 4,629,701 provides the desired resolved form of the carboxylic acids of formula I where R.sub.1 is acyl by subjecting an ester of the formula ##STR9## to an enzyme capable of asymmetrically hydrolyzing such an ester. It was found that while the ##STR10## moiety is hydrolyzed to the acid form, the racemic ester is also resolved into the S or R configuration in improved yields and at lower costs than possible with chemical resolution techniques. However, there is still a considerable expense in making these ester starting materials and higher optical purity is still desired for more active products. Therefore, a process which is less expensive with improved yields and which provides enhanced optical purity would be a useful addition to the art.